Lon protease plays a major role in the protein quality control system in mammalian cell mitochondria. It is present in the mitochondrial matrix, and degrades oxidized and misfolded proteins, thereby protecting the cell from various extracellular stresses, including oxidative stress. The intellectual disability-associated and thalidomide-binding protein cereblon (CRBN) contains a large, highly conserved Lon domain. However, whether CRBN has Lon protease-like function remains unknown. Here, we determined if CRBN has a protective function against oxidative stress, similar to Lon protease. We report that CRBN partially distributes in mitochondria, suggesting it has a mitochondrial function. To specify the mitochondrial role of CRBN, we mitochondrially expressed CRBN in human neuroblastoma SH-SY5Y cells. The resulting stable SH-SY5Y cell line showed no apparent effect on the mitochondrial functions of fusion, fission, and membrane potential. However, mitochondrially expressed CRBN exhibited protease activity, and was induced by oxidative stress. In addition, stably expressed cells exhibited suppressed neuronal cell death induced by hydrogen peroxide. These results suggest that CRBN functions specifically as a Lon-type protease in mitochondria.
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http://dx.doi.org/10.1038/srep29986 | DOI Listing |
Mol Med Rep
March 2025
Key Laboratory for Experimental Teratology of Ministry of Education, Department of Histology and Embryology, School of Basic Medical Sciences, Shandong University, Jinan, Shandong 250012, P.R. China.
Endometriosis (EM) is a chronic inflammatory disease that is one of the most common causes of gynecological systemic lesions in women before menopause. The most representative histological feature of EM is that the endometrium appears outside of the uterine cavity, often in the ovary. Although it is generally accepted that the epithelial and stromal cells of the ectopic endometrium are not malignant, they still have numerous similarities to malignant tumors, including considerable changes to the immune microenvironment (immune monitoring disorder), the creation of a specific hormone environment, high levels of oxidative stress, chronic inflammation and abnormal immune cell regulation.
View Article and Find Full Text PDFJ Biochem Mol Toxicol
January 2025
Department of Biochemistry (Medicine), Institute of Health Sciences, Aydın Adnan Menderes University, Aydin, Turkey.
The aim of this study was to investigate the potential role of thymoquinone in the treatment of inflammatory bowel disease (IBD) by examining the effects of various doses of thymoquinone on histopathological changes, oxidative stress, and antioxidant markers in basic stamens in a 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced colitis model in rats. Thirty-two rats were divided into four groups: control, TNBS, thymoquinone-20 (20 mg/kg), and thymoquinone-50 (50 mg/kg) groups. The basic stamens of 32 rats were used for this experiment.
View Article and Find Full Text PDFJ Biochem Mol Toxicol
January 2025
Intensive Care Unit, The Third Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China.
Sevoflurane (Sev) has a cardioprotective role in myocardial ischemia/reperfusion injury (MI/RI), but its mechanism has not been fully elucidated. This study aimed to investigate whether the circ_CDR1as/miR-671-5p/HMGA1 axis mediates the cardioprotective effect of Sev in MI/RI. Cardiomyocytes underwent hypoxia/reoxygenation (H/R) treatment was used to simulate MI/RI in vitro.
View Article and Find Full Text PDFJ Biochem Mol Toxicol
January 2025
Department of General Medicine, the Second Affiliated Hospital of Xi'an Jiaotong University, Xinjiang Hospital, Urumqi, China.
Among the diabetes-related complications, diabetic nephropathy is the major complication and it leads to end-stage renal failure. In the current investigation, we examined the protection of brucine, an alkaloid extracted from the seeds of Strychnos nux vomica plant widely used in traditional Chinese and Indian medicines against diabetic-induced nephropathy. Male Wistar rats were divided into four groups: control, diabetic rats, diabetic-induced + 40 mg/kg brucine-treated rats, and diabetic-induced + 25 mg/kg metformin-treated rats.
View Article and Find Full Text PDFToxicol Rep
December 2024
Department of Zoology, School of Sciences, IFTM University, Moradabad, Uttar Pradesh, India.
The effect of EMS at final concentration of 0.09, 0.18, 0.
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